Modulation of mitochondrial morphology by bioenergetics defects in primary human fibroblasts
Modulation of mitochondrial morphology by bioenergetics defects in primary human fibroblasts
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DOI：
10.1016/j.nmd.2007.12.008
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发表时间：
2008-04-01
影响因子：
2.8
通讯作者：
Lombes, A.
中科院分区：
文献类型：
--
作者：
Guillery, O.;Malka, F.;Lombes, A.
线粒体是一种不断融合和分裂的动态细胞器，这种融合和分裂的平衡导致了线粒体的形态。有证据表明，线粒体动力学和氧化磷酸化之间存在着错综复杂的关系，我们研究了生物能量学调制的线粒体形态在5个控制培养的原代皮肤成纤维细胞和7个氧化磷酸化的遗传改变。在基础条件下，控制成纤维细胞基本上是丝状线粒体。针对复合物I，III，IV或V的药物的氧化磷酸化抑制诱导部分但显著的线粒体片段化，而线粒体膜电位（DPSI m）的耗散引起完全片段化，糖酵解抑制没有影响。氧化磷酸化缺陷的成纤维细胞基本上正常的丝状线粒体在基础条件下，虽然当挑战时，他们中的一些人提出了轻微的改变裂变或融合的效力。严重缺陷的细胞在糖酵解抑制下显示线粒体完全断裂。总之，线粒体形态受D Psim调节，但与线粒体氧化磷酸化松散相关。它的糖酵解的改变，抑制指向一个严重的氧化磷酸化缺陷。(C)2008 Elsevier B.V.保留所有权利。
Mitochondria are dynamic organelles with continuous fusion and fission, the equilibrium of which results in mitochondrial morphology. Evidence points to there being an intricate relationship between mitochondrial dynamics and oxidative phosphorylation.We investigated the bioenergetics modulation of mitochondrial morphology in five control cultured primary skin fibroblasts and seven with genetic alterations of oxidative phosphorylation. Under basal conditions, control fibroblasts had essentially filamentous mitochondria. Oxidative phosphorylation inhibition with drugs targeting complex I, III, IV or V induced partial but significant mitochondrial fragmentation, whereas dissipation of mitochondrial membrane potential (D Psi m) provoked complete fragmentation, and glycolysis inhibition had no effect. Oxidative phosphorylation defective fibroblasts had essentially normal filamentous mitochondria under basal conditions, although when challenged some of them presented with mild alteration of fission or fusion efficacy. Severely defective cells disclosed complete mitochondrial fragmentation under glycolysis inhibition.In conclusion, mitochondrial morphology is modulated by D Psi m but loosely linked to mitochondrial oxidative phosphorylation. Its alteration by glycolysis, inhibition points to a severe oxidative phosphorylation defect. (C) 2008 Elsevier B.V. All rights reserved.